Surufatinib Monotherapy Shows Moderate Efficacy in Biliary Tract Carcinoma


A phase 2 study of surufatinib in patients with biliary tract carcinoma showed some benefit and a larger phase 3 study is underway.

The experimental small-molecule VEGFR inhibitor surufatinib yielded modest clinical benefits for patients with unresectable or metastatic biliary tract carcinoma, according to a report published recently in Cancer.

Notable results from the multicenter, single-arm, open-label phase 2 study included a 16-week progression-free survival (PFS) rate of 46.33% (95% Confidence Interval [CI], 24.38-65.73). In addition to this primary endpoint, results related to secondary endpoints included a median PFS of 3.7 months and a median overall survival (OS) of 6.9 months.

The best overall response was stable disease (SD) at week 16, achieved by nearly 1 in 4 patients (8 of 33; 24.2%). All patients were evaluable, and no patients had achieved a complete response (CR) or partial response (PR) by that time.

“When applied in the treatment of patients with BTC, surufatinib monotherapy has offered moderate clinical efficacy and shown expected tolerability and safety profiles,” wrote the authors, led by Jianming Xu, MD, of the Fifth Medical Center, General Hospital of the People’s Liberation Army, Beijing, China

This trial enrolled 39 patients in multiple centers in China. Nearly all patients (97.4%) had stage 4 disease at diagnosis. Intrahepatic cholangiocarcinoma was the most common malignancy, diagnosed in 29 patients (74.4%). Five patients each had extrahepatic cholangiocarcinoma (12.8%) and gallbladder cancer (12.8%). All patients received surufatinib at a dose of 300 mg, administered once a day, in 28-day cycles until disease progression or other event. The study ended when the last patient completed their 6-month follow up assessment. By this time, all surviving patients had discontinued the study drug, with about a third citing intolerable toxicity (35.9%). Nearly as many patients had experienced disease progression by that time (28.2%).

Subgroup analysis showed that the intrahepatic cholangiocarcinoma subgroup had a slightly longer median PFS of 3.7 months (95% CI, 2.1-6.5), compared with 2.9 months (95% CI, 1.9 to not reached [NR]) in the extrahepatic cholangiocarcinoma/gallbladder cancer subgroup (HR, 0.537; 95% CI, 0.200-1.440]. Median subgroup OS was similar, with 6.9 months (95% CI, 5.1-8.7) in the intrahepatic group and 6.4 months (95% CI, 2.4-NR) in the extrahepatic/gallbladder group (HR, 0.850; 95% CI, 0.375-1.923).

All 39 patients were included in the safety analysis and all but one experienced at least one treatment-related adverse event (AE) of any grade. The most common grade ≥ 3 treatment-related AEs were blood bilirubin increased (20.5%), hypertension (17.9%), and proteinuria (12.8%). These treatment-related AEs were observed at similar rates between subgroups: 72.4% in the intrahepatic disease group and 60.0% in the extrahepatic/gallbladder disease group. Two patients died during the trial; of these, investigators determined that one patient’s fatal cerebral hemorrhage was related to surufatinib treatment. The other patient’s fatal metabolic acidosis and cachexia were deemed unrelated to treatment.

In a post hoc analysis, the authors observed different clinical effects when patients with the CA 19-9 serum tumor marker received surufatinib as a second-line treatment. Patients with lower baseline values of CA 19-9 (≤ 1000 IU/mL) showed a higher 16-week PFS rate compared with patients who had higher baseline CA 19-9 levels: 52.4% (95% CI, 23.9-74.7) vs. 21.9% (95% CI, 1.2-59.3). The same was also true for median PFS: 3.3 months (95% CI, 1.6-4.1) versus 5.1 months (95% CI, 2.1-7.4).

“Results from subgroup and post hoc analyses revealed that patients with the proper [intrahepatic] tumor locations or appropriate levels of serum biomarkers might receive greater clinical benefits,” they wrote.

The same authors are currently running a larger phase 3 study of surufatinib in a larger biliary tract carcinoma population (NCT03873532).


Xu J, Bai Y, Sun H et al. A Single-Arm, Multicenter, Open-Label Phase 2 Trial of Surufatinib in Patients with Unresectable or Metastatic Biliary Tract Cancer. Cancer. 2021;127:3975-3984.

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